4CZ4

HP24stab derived from the villin headpiece subdomain

4CZ4 の概要

• エントリーDOI: 10.2210/pdb4cz4/pdb
• 関連するPDBエントリー: 4CZ3
• NMR情報: BMRB: 19929
• 分子名称: VILLIN-1 (1 entity in total)
• 機能のキーワード: actin-binding protein, villin, subdomain, supersecondary, chicken, hyperstable
• 由来する生物種: GALLUS GALLUS (CHICKEN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2837.43

構造登録者

Hocking, H.,Haese, F.,Madl, T.,Zacharias, M.,Rief, M.,Zoldak, G. (登録日: 2014-04-16, 公開日: 2015-02-18, 最終更新日: 2024-11-20)

主引用文献

Hocking, H.G.,Hase, F.,Madl, T.,Zacharias, M.,Rief, M.,Zoldak, G.
A Compact Native 24-Residue Supersecondary Structure Derived from the Villin Headpiece Subdomain.
Biophys.J., 108:678-, 2015

PubMed Abstract: Many small proteins fold highly cooperatively in an all-or-none fashion and thus their native states are well protected from thermal fluctuations by an extensive network of interactions across the folded structure. Because protein structures are stabilized by local and nonlocal interactions among distal residues, dissecting individual substructures from the context of folded proteins results in large destabilization and loss of unique three-dimensional structure. Thus, mini-protein substructures can only rarely be derived from natural templates. Here, we describe a compact native 24-residues-long supersecondary structure derived from the hyperstable villin headpiece subdomain consisting of helices 2 and 3 (HP24). Using a combination of experimental techniques, including NMR and small-angle x-ray scattering, as well as all-atom replica exchange molecular-dynamics simulations, we show that a variant with stabilizing substitutions (HP24stab) forms a densely packed and compact conformation. In HP24stab, interactions between helices 2 and 3 are similar to those observed in native folded HP35, and the two helices cooperatively stabilize each other by completing the hydrophobic core lining the central part of HP35. Interestingly, even though the HP24wt fragment shows a more expanded and less structured conformation, NMR and simulations demonstrate a preference for a native-like topology. Thus, the two stabilizing residues in HP24stab shift the energy balance toward the native state, leading to a minimal folding motif.

PubMed: 25650934
DOI: 10.1016/J.BPJ.2014.11.3482

実験手法

SOLUTION NMR